Introduction: Recent advance of genetic testing has contributed to the diagnosis of hereditary pheochromocytoma and paraganglioma (PPGL). Germline mutations in MYC associated factor X(MAX) are responsible for 1.1% of these PPGL; the median age at onset is 33 years and no reliable penetrance estimation is available for MAX-carriers. The authors present the case of a synchronous bilateral pheochromocytoma that prompted the discovery of a proband of MAX mutation and three other relatives affected. Case presentation: Male, 33 years old, healthy until May′1994 when he was diagnosed with hypertension; he was started on anti-hypertensive drugs but blood pressure (BP) remained uncontrolled. Simultaneously, he initiated paroxysms of headaches, diaphoresis and pallor that lasted less than 5 minutes and occurred at least twice daily. He was observed at our Endocrinology outpatient clinic in March′1995. Other than a BP of 170/100 mmHg he had no abnormality on physical examination. Our investigation revealed elevated 24 hour-urinary catecholamines (noradrenaline 11754 nmol [25× upper limit of normal range (ULN)], adrenaline 239 nmol [2.2ULN] and dopamine 3668 nmol [1.4ULN]) and metanephrines (normetanephrine 1.36 mg (1.36 ULN) and metanephrine0.54 mg (1.35 ULN). Abdominal-CT revealed two round shaped adrenal lesions (one at each adrenal gland) measuring 2.5 cm in diameter with smooth and well-defined margins, no evidence of metastasis; 123I-MIBG showed bilateral trace uptake. MEN-2 was excluded and genetic testing for RET mutation was negative. He was submitted to right total adrenalectomy and left subtotal adrenalectomy on May1995; pathological findings indicated bilateral hyperplasia. Normal urinary catecholamines and fractionated metanephrines until June1996, when he presented with clinical and biochemical evidence of catecholamine excess and imaging compatible with a residual lesion on the left adrenal gland. Left total adrenalectomy on June2000.This time, anatomopathological examination was consistentwith pheocromocytoma and until now he has no clinical or biochemical evidence of catecholamines excess or relapse. A multigene panel- search revealed a truncating MAX mutation affecting exon 3(c.97C>T). We evaluated all the probands relatives and discovered the same MAX mutation with bilateral adrenal mass and evidence of catecholamine excess in all three of the probands sons; the older son died in 2014 from malign pheocromocytomawith unresectable metastasis. The two younger sons have refused surgery and remain under surveillance.
Conclusions: In face of a patient with bilateral pheocromocytoma, hereditary aetiology must always be considered. Once a mutation is identified in the family, molecular testing of the relatives must be offered.
18 - 21 May 2019
European Society of Endocrinology